Cdon Acts As a Hedgehog Decoy Receptor During Proximal-Distal Patterning of the Optic Vesicle
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The Morphogenesis of the Zebrafish Eye, Including a Fate Map of The
DEVELOPMENTAL DYNAMICS 218:175–188 (2000) The Morphogenesis of the Zebrafish Eye, Including a Fate Map of the Optic Vesicle ZHENG LI, NANCY M. JOSEPH, AND STEPHEN S. EASTER, JR.* Biology Department, University of Michigan, Ann Arbor, Michigan ABSTRACT We have examined the morpho- The morphogenesis of the zebrafish eye, described by genesis of the zebrafish eye, from the flat optic Schmitt and Dowling (1994), is similar, but different in vesicle at 16 hours post fertilization (hpf) to the some respects. Their scanning electron micrographs of functional hemispheric eye at 72 hpf. We have skinned embryos provided excellent views of the eye, produced three-dimensional reconstructions and revealed that the vesicle bypassed the spherical from semithin sections, measured volumes and stage; when discerned at about 14 hours post fertiliza- areas, and produced a fate map by labeling clus- tion (hpf), the vesicle was a flattened wing-like struc- ters of cells at 14–15 hpf and finding them in the ture. The “wing” was initially attached to the neural 24 hpf eye cup. Both volume and area increased tube over most of its length, but by 16 hpf had detached sevenfold, with different schedules. Initially from most of the neural tube, the only remaining point (16–33 hpf), area increased but volume remained of attachment through the optic stalk. The vesicle constant; later (33–72 hpf) both increased. When sagged, so that its erstwhile dorsal and ventral sur- the volume remained constant, the presumptive faces faced laterally and medially, respectively, and the pigmented epithelium (PE) shrank and the pre- choroid fissure formed, but caudal to the optic stalk, sumptive neural retina (NR) enlarged. -
Supplemental Tables4.Pdf
Yano_Supplemental_Table_S4 Gene ontology – Biological process 1 of 9 Fold List Pop Pop GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment DLC1, CADM1, NELL2, CLSTN1, PCDHGA8, CTNNB1, NRCAM, APP, CNTNAP2, FERT2, RAPGEF1, PTPRM, MPDZ, SDK1, PCDH9, PTPRS, VEZT, NRXN1, MYH9, GO:0007155~cell CTNNA2, NCAM1, NCAM2, DDR1, LSAMP, CNTN1, 50 5.61 2.14E-08 510 311 7436 2.34 4.50E-05 4.50E-05 3.70E-05 adhesion ROR2, VCAN, DST, LIMS1, TNC, ASTN1, CTNND2, CTNND1, CDH2, NEO1, CDH4, CD24A, FAT3, PVRL3, TRO, TTYH1, MLLT4, LPP, NLGN1, PCDH19, LAMA1, ITGA9, CDH13, CDON, PSPC1 DLC1, CADM1, NELL2, CLSTN1, PCDHGA8, CTNNB1, NRCAM, APP, CNTNAP2, FERT2, RAPGEF1, PTPRM, MPDZ, SDK1, PCDH9, PTPRS, VEZT, NRXN1, MYH9, GO:0022610~biological CTNNA2, NCAM1, NCAM2, DDR1, LSAMP, CNTN1, 50 5.61 2.14E-08 510 311 7436 2.34 4.50E-05 4.50E-05 3.70E-05 adhesion ROR2, VCAN, DST, LIMS1, TNC, ASTN1, CTNND2, CTNND1, CDH2, NEO1, CDH4, CD24A, FAT3, PVRL3, TRO, TTYH1, MLLT4, LPP, NLGN1, PCDH19, LAMA1, ITGA9, CDH13, CDON, PSPC1 DCC, ENAH, PLXNA2, CAPZA2, ATP5B, ASTN1, PAX6, ZEB2, CDH2, CDH4, GLI3, CD24A, EPHB1, NRCAM, GO:0006928~cell CTTNBP2, EDNRB, APP, PTK2, ETV1, CLASP2, STRBP, 36 4.04 3.46E-07 510 205 7436 2.56 7.28E-04 3.64E-04 5.98E-04 motion NRG1, DCLK1, PLAT, SGPL1, TGFBR1, EVL, MYH9, YWHAE, NCKAP1, CTNNA2, SEMA6A, EPHA4, NDEL1, FYN, LRP6 PLXNA2, ADCY5, PAX6, GLI3, CTNNB1, LPHN2, EDNRB, LPHN3, APP, CSNK2A1, GPR45, NRG1, RAPGEF1, WWOX, SGPL1, TLE4, SPEN, NCAM1, DDR1, GRB10, GRM3, GNAQ, HIPK1, GNB1, HIPK2, PYGO1, GO:0007166~cell RNF138, ROR2, CNTN1, -
<I>BOC</I> Is a Modifier Gene in Holoprosencephaly
Received: 12 May 2017 Revised: 20 June 2017 Accepted: 28 June 2017 DOI: 10.1002/humu.23286 BRIEF REPORT BOC is a modifier gene in holoprosencephaly Mingi Hong1∗ Kshitij Srivastava2∗ Sungjin Kim1 Benjamin L. Allen3 Daniel J. Leahy4 Ping Hu2 Erich Roessler2 Robert S. Krauss1† Maximilian Muenke2† 1Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 2Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 3Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 4Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas Correspondence Robert S. Krauss (for editorial communication), Abstract Department of Cell, Developmental and Regen- Holoprosencephaly (HPE), a common developmental defect of the forebrain and midface, has a erative Biology, Icahn School of Medicine at complex etiology. Heterozygous, loss-of-function mutations in the sonic hedgehog (SHH) pathway Mount Sinai, New York, New York 10029. Email: [email protected] are associated with HPE. However, mutation carriers display highly variable clinical presentation, Maximilian Muenke, Medical Genetics Branch, leading to an “autosomal dominant with modifier” model, in which the penetrance and expressiv- National Human Genome Research Institute, ity of a predisposing mutation is graded by genetic or environmental modifiers. Such modifiers National Institutes of Health, Bethesda, Mary- land 20892. have not been identified. Boc encodes a SHH coreceptor and is a silent HPE modifier gene in mice. Email: [email protected] Here, we report the identification of missense BOC variants in HPE patients. Consistent with these ∗Mingi Hong and Kshitij Srivastava contributed alleles functioning as HPE modifiers, individual variant BOC proteins had either loss- or gain-of- equally to this work. -
Hedgehog Signaling, Epithelial-To-Mesenchymal Transition and Mirna (Review)
271-275 1/8/08 15:18 Page 271 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22: 271-275, 2008 271 Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA (Review) YURIKO KATOH1 and MASARU KATOH2 1M&M Medical Bioinformatics, Hongo 113-0033; 2Genetics and Cell Biology Section, National Cancer Center, Tokyo 104-0045, Japan Received May 19, 2008; Accepted June 26, 2008 DOI: 10.3892/ijmm_00000019 Abstract. SHH, IHH, and DHH are lipid-modified secreted strictly controlled before clinical application of synthetic proteins binding to Patched receptors, and CDON, BOC or miRNA. Peptide mimetic and RNA aptamer could also be GAS1 co-receptors. In the absence of Hedgehog signaling, utilized as Hedgehog signaling inhibitors or EMT suppressors. GLI1 is transcriptionally repressed, GLI2 is phosphorylated by GSK3 and CK1 for the FBXW11 (ßTRCP2)-mediated degradation, and GLI3 is processed to a cleaved repressor. In Contents the presence of Hedgehog signaling, Smoothened is relieved from Patched-mediated suppression due to the Hedgehog- 1. Introduction dependent internalization of Patched, which leads to 2. Hedgehog signaling pathway MAP3K10 (MST) activation and SUFU inactivation for the 3. Epithelial-to-mesenchymal transition (EMT) stabilization and nuclear accumulation of GLI family 4. Hedgehog and EMT members. GLI activators then upregulate CCND1, CCND2 5. MicroRNA (miRNA) for cell cycle acceleration, FOXA2, FOXC2, FOXE1, 6. Perspectives FOXF1, FOXL1, FOXP3, POU3F1, RUNX2, SOX13, TBX2 for cell fate determination, JAG2, INHBC, and INHBE for 1. Introduction stem cell signaling regulation. Hedgehog signals also up- regulate SFRP1 in mesenchymal cells for WNT signaling Hedgehog family members are key regulators of embryo- regulation. Epithelial-to-mesenchymal transition (EMT) during genesis, adult tissue homeostasis, and carcinogenesis (1-5). -
Embryology, Anatomy, and Physiology of the Afferent Visual Pathway
CHAPTER 1 Embryology, Anatomy, and Physiology of the Afferent Visual Pathway Joseph F. Rizzo III RETINA Physiology Embryology of the Eye and Retina Blood Supply Basic Anatomy and Physiology POSTGENICULATE VISUAL SENSORY PATHWAYS Overview of Retinal Outflow: Parallel Pathways Embryology OPTIC NERVE Anatomy of the Optic Radiations Embryology Blood Supply General Anatomy CORTICAL VISUAL AREAS Optic Nerve Blood Supply Cortical Area V1 Optic Nerve Sheaths Cortical Area V2 Optic Nerve Axons Cortical Areas V3 and V3A OPTIC CHIASM Dorsal and Ventral Visual Streams Embryology Cortical Area V5 Gross Anatomy of the Chiasm and Perichiasmal Region Cortical Area V4 Organization of Nerve Fibers within the Optic Chiasm Area TE Blood Supply Cortical Area V6 OPTIC TRACT OTHER CEREBRAL AREASCONTRIBUTING TO VISUAL LATERAL GENICULATE NUCLEUSPERCEPTION Anatomic and Functional Organization The brain devotes more cells and connections to vision lular, magnocellular, and koniocellular pathways—each of than any other sense or motor function. This chapter presents which contributes to visual processing at the primary visual an overview of the development, anatomy, and physiology cortex. Beyond the primary visual cortex, two streams of of this extremely complex but fascinating system. Of neces- information flow develop: the dorsal stream, primarily for sity, the subject matter is greatly abridged, although special detection of where objects are and for motion perception, attention is given to principles that relate to clinical neuro- and the ventral stream, primarily for detection of what ophthalmology. objects are (including their color, depth, and form). At Light initiates a cascade of cellular responses in the retina every level of the visual system, however, information that begins as a slow, graded response of the photoreceptors among these ‘‘parallel’’ pathways is shared by intercellular, and transforms into a volley of coordinated action potentials thalamic-cortical, and intercortical connections. -
Mutations in CDON, Encoding a Hedgehog Receptor, Result in Holoprosencephaly and Defective Interactions with Other Hedgehog Receptors
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector ARTICLE Mutations in CDON, Encoding a Hedgehog Receptor, Result in Holoprosencephaly and Defective Interactions with Other Hedgehog Receptors Gyu-Un Bae,1,2,4,6 Sabina Domene´,3,4,7 Erich Roessler,3 Karen Schachter,1,8 Jong-Sun Kang,2,5,* Maximilian Muenke,3,5,* and Robert S. Krauss1,5 Holoprosencephaly (HPE), a common human congenital anomaly defined by a failure to delineate the midline of the forebrain and/or midface, is associated with diminished Sonic hedgehog (SHH)-pathway activity in development of these structures. SHH signaling is regulated by a network of ligand-binding factors, including the primary receptor PTCH1 and the putative coreceptors, CDON (also called CDO), BOC, and GAS1. Although binding of SHH to these receptors promotes pathway activity, it is not known whether interactions between these receptors are important. We report here identification of missense CDON mutations in human HPE. These mutations diminish CDON’s ability to support SHH-dependent gene expression in cell-based signaling assays. The mutations occur outside the SHH-binding domain of CDON, and the encoded variant CDON proteins do not display defects in binding to SHH. In contrast, wild-type CDON associates with PTCH1 and GAS1, but the variants do so inefficiently, in a manner that parallels their activity in cell-based assays. Our findings argue that CDON must associate with both ligand and other hedgehog-receptor components, particularly PTCH1, for signaling to occur and that disruption of the latter interactions is a mechanism of HPE. -
Role of Cytonemes in Wnt Transport Eliana Stanganello and Steffen Scholpp*
© 2016. Published by The Company of Biologists Ltd | Journal of Cell Science (2016) 129, 665-672 doi:10.1242/jcs.182469 COMMENTARY Role of cytonemes in Wnt transport Eliana Stanganello and Steffen Scholpp* ABSTRACT dependent or canonical Wnt signaling (reviewed in Logan and Wnt signaling regulates a broad variety of processes during Nusse, 2004). Paracrine signaling activity is fundamental to the embryonic development and disease. A hallmark of the Wnt morphogenetic function of Wnt proteins in tissue patterning. signaling pathway is the formation of concentration gradients by However, the extracellular transport mechanism of this morphogen Wnt proteins across responsive tissues, which determines cell fate from the signal-releasing cell to the recipient cell is still debated. in invertebrates and vertebrates. To fulfill its paracrine function, Recent data suggest that Wnt proteins are distributed on long trafficking of the Wnt morphogen from an origin cell to a recipient cell signaling filopodia known as cytonemes, which allow contact- must be tightly regulated. A variety of models have been proposed to dependent, juxtacrine signaling over a considerable distance. We explain the extracellular transport of these lipid-modified signaling have recently shown that, in zebrafish, Wnt8a is transported on proteins in the aqueous extracellular space; however, there is still actin-containing cytonemes to cells, where it activates the signaling considerable debate with regard to which mechanisms allow the required for the specification of neural plate cells (Stanganello et al., precise distribution of ligand in order to generate a morphogenetic 2015). Concomitantly, the Wnt receptor Frz was identified on gradient within growing tissue. Recent evidence suggests that Wnt cytonemes to enable the retrograde transport of Wnt proteins on proteins are distributed along signaling filopodia during vertebrate these protrusions during flight muscle formation in Drosophila and invertebrate embryogenesis. -
Bmps and Ventral Optic Cup Differentiation 3163
Development 129, 3161-3171 (2002) 3161 Printed in Great Britain © The Company of Biologists Limited 2002 DEV1795 The role of bone morphogenetic proteins in the differentiation of the ventral optic cup Ruben Adler1 and Teri L. Belecky-Adams2,* 1The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA 2Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA *Author for correspondence (e-mail: [email protected]) Accepted 20 March 2002 SUMMARY The ventral region of the chick embryo optic cup undergoes stages of development, this treatment resulted in a complex process of differentiation leading to the microphthalmia with concomitant disruption of the formation of four different structures: the neural retina, developing neural retina, RPE and lens. At optic cup the retinal pigment epithelium (RPE), the optic disk/optic stages, however, noggin overexpression caused colobomas, stalk, and the pecten oculi. Signaling molecules such as pecten agenesis, replacement of the ventral RPE by retinoic acid and sonic hedgehog have been implicated neuroepithelium-like tissue, and ectopic expression of optic in the regulation of these phenomena. We have now stalk markers in the region of the ventral retina and RPE. investigated whether the bone morphogenetic proteins This was frequently accompanied by abnormal growth of (BMPs) also regulate ventral optic cup development. Loss- ganglion cell axons, which failed to enter the optic nerve. of-function experiments were carried out in chick embryos The data suggest that endogenous BMPs have significant in ovo, by intraocular overexpression of noggin, a protein effects on the development of ventral optic cup structures. that binds several BMPs and prevents their interactions with their cognate cell surface receptors. -
"The Genecards Suite: from Gene Data Mining to Disease Genome Sequence Analyses". In: Current Protocols in Bioinformat
The GeneCards Suite: From Gene Data UNIT 1.30 Mining to Disease Genome Sequence Analyses Gil Stelzer,1,5 Naomi Rosen,1,5 Inbar Plaschkes,1,2 Shahar Zimmerman,1 Michal Twik,1 Simon Fishilevich,1 Tsippi Iny Stein,1 Ron Nudel,1 Iris Lieder,2 Yaron Mazor,2 Sergey Kaplan,2 Dvir Dahary,2,4 David Warshawsky,3 Yaron Guan-Golan,3 Asher Kohn,3 Noa Rappaport,1 Marilyn Safran,1 and Doron Lancet1,6 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel 2LifeMap Sciences Ltd., Tel Aviv, Israel 3LifeMap Sciences Inc., Marshfield, Massachusetts 4Toldot Genetics Ltd., Hod Hasharon, Israel 5These authors contributed equally to the paper 6Corresponding author GeneCards, the human gene compendium, enables researchers to effectively navigate and inter-relate the wide universe of human genes, diseases, variants, proteins, cells, and biological pathways. Our recently launched Version 4 has a revamped infrastructure facilitating faster data updates, better-targeted data queries, and friendlier user experience. It also provides a stronger foundation for the GeneCards suite of companion databases and analysis tools. Improved data unification includes gene-disease links via MalaCards and merged biological pathways via PathCards, as well as drug information and proteome expression. VarElect, another suite member, is a phenotype prioritizer for next-generation sequencing, leveraging the GeneCards and MalaCards knowledgebase. It au- tomatically infers direct and indirect scored associations between hundreds or even thousands of variant-containing genes and disease phenotype terms. Var- Elect’s capabilities, either independently or within TGex, our comprehensive variant analysis pipeline, help prepare for the challenge of clinical projects that involve thousands of exome/genome NGS analyses. -
PRMT7 Ablation in Cardiomyocytes Causes Cardiac Hypertrophy and Fibrosis Through Β-Catenin Dysregulation
PRMT7 Ablation in Cardiomyocytes Causes Cardiac Hypertrophy and Fibrosis Through β-Catenin Dysregulation Byeong-Yun Ahn Sungkyunkwan University School of Medicine Myong-Ho Jeong Sungkyunkwan University School of Medicine Jung-Hoon Pyun Sungkyunkwan University School of Medicine Hyeon-Ju Jeong Sungkyunkwan University School of Medicine Tuan Anh Vuong Sungkyunkwan University School of Medicine Ju-Hyeon Bae Sungkyunkwan University School of Medicine Subin An Sungkyunkwan University School of Medicine Su Woo Kim Sungkyunkwan University School of Medicine Yong Kee Kim Sookmyung Women's University Dongryeol Ryu Sungkyunkwan University School of Medicine Hyun-Ji Kim Sungkyunkwan University School of Medicine Hana Cho Sungkyunkwan University School of Medicine Gyu-Un Bae ( [email protected] ) Sookmyung Women's University College of Pharmacy https://orcid.org/0000-0003-4262-1895 Jong-Sun Kang Sungkyunkwan University School of Medicine Research Article Page 1/24 Keywords: PRMT7, cardiomyopathy, Wnt, β-Catenin Posted Date: August 19th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-798227/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/24 Abstract Angiotensin II (AngII) has potent cardiac hypertrophic effects mediated through activation of hypertrophic signaling like Wnt/b-Catenin signaling. In the current study, we examined the role of protein arginine methyltransferase 7 (PRMT7) in cardiac function. PRMT7 was greatly decreased in hypertrophic hearts chronically infused with AngII and cardiomyocytes treated with AngII. PRMT7 depletion in rat cardiomyocytes resulted in hypertrophic responses. Consistently, mice lacking PRMT7 exhibited displayed the cardiac hypertrophy and brosis. PRMT7 overexpression abrogated the cellular hypertrophy elicited by AngII, while PRMT7 depletion exacerbated the hypertrophic response caused by AngII. -
Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis
Downloaded from http://cshperspectives.cshlp.org/ on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis Robert S. Krauss, Giselle A. Joseph, and Aviva J. Goel Department of Cell, Developmental, and Regenerative Biology, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029 Correspondence: [email protected] Development of skeletal muscle is a multistage process that includes lineage commitment of multipotent progenitor cells, differentiation and fusion of myoblasts into multinucleated myofibers, and maturation of myofibers into distinct types. Lineage-specific transcriptional regulation lies at the core of this process, but myogenesis is also regulated by extracellular cues. Some of these cues are initiated by direct cell–cell contact between muscle precursor cells themselves or between muscle precursors and cells of other lineages. Examples of the latter include interaction of migrating neural crest cells with multipotent muscle progenitor cells, muscle interstitial cells with myoblasts, and neurons with myofibers. Among the sig- naling factors involved are Notch ligands and receptors, cadherins, Ig superfamily members, and Ephrins and Eph receptors. In this article we describe recent progress in this area and highlight open questions raised by the findings. keletal muscle is the most abundant tissue in based on expression of distinct myosin heavy Sthe vertebrate body and necessary for breath- chain (MyHC) isoforms and metabolic capabil- ing, metabolic homeostasis, and locomotion. ities (Schiaffino and Reggiani 2011; Talbot and Development of skeletal muscle occurs in a se- Maves 2016). quential, multistage process that includes spec- Myogenic specification and differentiation ification of multipotent progenitors to lineage- are coordinated by the myogenic basic helix– committed myoblasts, differentiation of myo- loop–helix (bHLH) transcription factors Myf5, blasts into multinucleated myofibers, and mat- MyoD, myogenin, and MRF4. -
Molecular Regulation of Visual System Development: More Than Meets the Eye
Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Molecular regulation of visual system development: more than meets the eye Takayuki Harada,1,2 Chikako Harada,1,2 and Luis F. Parada1,3 1Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA; 2Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan Vertebrate eye development has been an excellent model toderm, intercalating mesoderm, surface ectoderm, and system to investigate basic concepts of developmental neural crest (Fig. 1). The neuroectoderm differentiates biology ranging from mechanisms of tissue induction to into the retina, iris, and optic nerve; the surface ecto- the complex patterning and bidimensional orientation of derm gives rise to lens and corneal epithelium; the me- the highly specialized retina. Recent advances have shed soderm differentiates into the extraocular muscles and light on the interplay between numerous transcriptional the fibrous and vascular coats of the eye; and neural crest networks and growth factors that are involved in the cells become the corneal stroma sclera and corneal en- specific stages of retinogenesis, optic nerve formation, dothelium. The vertebrate eye originates from bilateral and topographic mapping. In this review, we summarize telencephalic optic grooves. In humans, optic vesicles this recent progress on the molecular mechanisms un- emerge at the end of the fourth week of development and derlying the development of the eye, visual system, and soon thereafter contact the surface ectoderm to induce embryonic tumors that arise in the optic system.